The proposed research involves the total synthesis of (-)-Terpestacin, a cellular inhibitor of the HIV virus. The primary goal is a brief, convergent synthesis anchored upon two powerful methodologies, asymmetric cyclopentannelation and ring closing metathesis. Asymmetric cyclopentannelation, developed by the Tius group, delivers complex chiral cyclopentanones, the core of Terpestacin. The target will be assembled in two pieces to be connected late in the synthesis and then cyclized using olefin metathesis. Asymmetric cyclopentannelation has demonstrated remarkable potential at delivering complex chiral cyclopentanones rapidly and in high stereopurity. The methodology is under continuing refinement including the development of new more powerful chiral auxiliaries for which this project serves as an excellent application. Ring closing metathesis has quickly become a mainstay method of macrocyclization. Some of the major challenges that still exist are the directing the regiospecificity of the olefination in the presence of competing reacting alkenes as well as the manipulation of the stereoselectivity of the final alkene formation. This proposed synthetic route would culminate with the olefination of two resident olefins in the presence of others. The selectivity for the desired olefination is based upon steric manipulations introduced by the Nicolaou group. This project represents an extended proving ground for this strategy of regiocontrol. Finally, the project represents a nice dichotomy of methodology development and total synthesis culminating in a rapid means of producing this possible anti-HIV drug. [unreadable] [unreadable]